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Trends Pharmacol Sci. 2017 Apr;38(4):363-377. doi: 10.1016/j.tips.2016.12.006. Epub 2017 Jan 28.

Targeting Class I Histone Deacetylases in a "Complex" Environment.

Author information

1
Henry Wellcome Laboratories of Structural Biology, Department of Molecular and Cell Biology, University of Leicester, Lancaster Road, Leicester LE1 9HN, UK.
2
Henry Wellcome Laboratories of Structural Biology, Department of Molecular and Cell Biology, University of Leicester, Lancaster Road, Leicester LE1 9HN, UK. Electronic address: john.schwabe@le.ac.uk.

Abstract

Histone deacetylase (HDAC) inhibitors are proven anticancer therapeutics and have potential in the treatment of many other diseases including HIV infection, Alzheimer's disease, and Friedreich's ataxia. A problem with the currently available HDAC inhibitors is that they have limited specificity and target multiple deacetylases. Designing isoform-selective inhibitors has proven challenging due to similarities in the structure and chemistry of HDAC active sites. However, the fact that HDACs 1, 2, and 3 are recruited to several large multi-subunit complexes, each with particular biological functions, raises the possibility of specifically inhibiting individual complexes. This may be assisted by recent structural and functional information about the assembly of these complexes. Here, we review the available structural information and discuss potential targeting strategies.

KEYWORDS:

HDAC inhibitors; co-repressor complexes; gene regulation; histone deacetylases; inositol phosphates; transcription repression

PMID:
28139258
DOI:
10.1016/j.tips.2016.12.006
[Indexed for MEDLINE]

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